Clinical Efficacy
Life’s little victories start with profound seizure reduction
The safety and effectiveness of FINTEPLA for the treatment of seizures associated with Dravet syndrome were established in 2 randomized, double-blind, placebo-controlled trials (Study 1 and Study 2) in patients 2 to 18 years of age.
Results from Study 1 evaluating the safety and efficacy of FINTEPLA in patients with Dravet syndrome
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Study 1 (N=117) compared 0.7 and 0.2 mg/kg/day FINTEPLA with placebo in patients who were inadequately controlled on 1-4 concomitant antiepileptic drugs and had a minimum of 6 convulsive seizures during the baseline period. The primary efficacy endpoint was the change from baseline in the frequency of convulsive seizures per 28 days during the combined 14-week titration and maintenance periods (ie, treatment period). The median longest interval between convulsive seizures was also assessed.
FINTEPLA 0.7 mg/kg/day reduced monthly convulsive seizures a median of 79.4% from baseline over 14 weeks.1
- The placebo-adjusted percent reduction in monthly convulsive seizure frequency was 70.0% for FINTEPLA 0.7 mg/kg/day (P<.001) and 31.7% for FINTEPLA 0.2 mg/kg/day (P=.043)
- A reduction in convulsive seizures was observed within 3 to 4 weeks of starting FINTEPLA, and the effect remained generally consistent over the 14-week treatment period
Reduction in Convulsive Seizure Frequency From Baseline (Study 1)1
The majority of patients (70%) taking FINTEPLA 0.7 mg/kg/day over 14 weeks experienced a 50% or greater reduction in monthly convulsive seizures.
- 7 in 10 patients had a clinically meaningful (≥50%) reduction
- More than 1 in 2 patients had a profound (≥75%) reduction
Proportion of Patients Achieving ≥50% or ≥75% Reduction in Convulsive Seizures From Baseline (Study 1)
50% of patients taking FINTEPLA 0.7 mg/kg/day over 14 weeks achieved a seizure-free (0 seizures) interval lasting at least 21 days vs 8 days in the placebo group.
Patients in Study 1 had an average of 1.5 seizures per day at baseline.1
Median Longest Seizure-Free Interval (Study 1)
8% of patients taking FINTEPLA 0.7 mg/kg/day reported no convulsive seizures during the entire 14 weeks vs 0 patients in the placebo group.
Proportion of Patients Who Had 0 Seizures Over 14 Weeks (Study 1)
1 in 4 patients taking FINTEPLA 0.7 mg/kg/day had no more than a single seizure during the 14-week treatment period.1
- Because these results were obtained in a post hoc analysis, no conclusions of efficacy should be made
At baseline, patients in Study 1 experienced a mean of 41 seizures per month.1
Proportion of Patients Who Had 0 or 1 Seizure Over 14 Weeks (Study 1)1
FINTEPLA demonstrated significant efficacy when added to stiripentol
Results from Study 2 evaluating the safety and efficacy of FINTEPLA in patients with Dravet syndrome receiving stiripentol and either clobazam, valproate, or both
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Study 2 (N=85) compared 0.4 mg/kg/day FINTEPLA with placebo in patients who were inadequately controlled on 2-4 concomitant antiepileptic drugs (including stiripentol and either clobazam, valproate, or both) and had a minimum of 6 convulsive seizures during the baseline period. The primary efficacy endpoint was the change from baseline in the frequency of convulsive seizures per 28 days during the combined 15-week titration and maintenance periods (ie, treatment period). The median longest interval between convulsive seizures was also assessed. The 0.4 mg/kg/day dose was not an intermediate dose. Patients on the 0.4 mg/kg/day dose were also taking concomitant stiripentol (with clobazam and/or valproate), which increases exposure of FINTEPLA.
FINTEPLA 0.4 mg/kg/day reduced monthly convulsive seizures 63.1% from baseline.1
- The placebo-adjusted percent reduction in monthly convulsive seizure frequency was 59.5% (P<.001)
Reduction in Convulsive Seizure Frequency From Baseline (Study 2)1
All patients in both study groups were receiving stiripentol and either clobazam, valproate, or both.
The majority of patients (53.5%) taking FINTEPLA 0.4 mg/kg/day over 15 weeks experienced a 50% or greater reduction in monthly convulsive seizures.
- More than 1 in 3 patients experienced a 75% or greater reduction in convulsive seizures
Proportion of Patients Achieving ≥50% or ≥75% Reduction in Convulsive Seizures From Baseline (Study 2)
aP value vs placebo.
All patients in both study groups were receiving stiripentol and either clobazam, valproate, or both.
Long-term extension study
Results from a long-term (3-year), open-label extension study of FINTEPLA in patients with Dravet syndrome
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- 94% of patients who completed Study 1 or Study 2 participated in a long-term, flexible-dose, open-label extension study
- All patients were started at a dose of 0.2 mg/kg/day and were subsequently titrated up to their maintenance dose
- The results of this open-label, uncontrolled study are exploratory; therefore, no conclusions of efficacy should be made
In controlled and uncontrolled trials, 341 patients were treated with FINTEPLA, including 312 treated for >6 months, 284 for >1 year, and 138 for >2 years.
Reduction in Convulsive Seizure Frequency Over Time1
The number of patients assessed at each time point is shown in the figure. The decrease in patient number is primarily due to staggered entry into the study.
FINTEPLA study designs
The safety and effectiveness of FINTEPLA for the treatment of seizures associated with Dravet syndrome were established in 2 randomized, double-blind, placebo-controlled trials (Study 1 and Study 2) in patients 2 to 18 years of age.
Patient selection
Patients had a clinical diagnosis of Dravet syndrome and seizures that were inadequately controlled on at least 1 antiepileptic drug (AED) or treatment including vagal nerve stimulation or ketogenic diet.
Seizure types
Convulsive seizure types assessed included tonic, clonic, generalized tonic-clonic, tonic-atonic, secondarily generalized tonic-clonic, hemiclonic, and focal with observable motor signs.
| Study 1 (N=117) |
|
|---|---|
| Study groups | 0.7 mg/kg/daya 0.2 mg/kg/daya Placebo |
| Baseline convulsive seizure frequency | ≥6 over 6 weeks, with a mean of 41 (median of 22) per month1 |
| Concomitant AEDs | Stiripentol was not allowed in this study 98% of patients were taking 1-4 concomitant AEDs, including valproate (61%), clobazam (59%), and topiramate (25%) |
| Primary endpoint | Change from baseline in frequency of monthly convulsive seizures with FINTEPLA vs placebo |
aStudy 1 compared 2 doses of fenfluramine, 0.7 mg/kg/day and 0.2 mg/kg/day, with placebo in patients who were not receiving stiripentol.
| Study 2 (N=85) |
|
|---|---|
| Study groups | 0.4 mg/kg/dayb Placebo |
| Baseline convulsive seizure frequency | ≥6 over 6 weeks, with a mean of 26 (median of 12) per month1 |
| Concomitant AEDs | All patients were also on stiripentol 100% of patients were taking 2-4 concomitant AEDs, including stiripentol (100%), clobazam (94%), and valproate (89%) |
| Primary endpoint | Change from baseline in frequency of monthly convulsive seizures with FINTEPLA vs placebo |
bStudy 2 compared 1 dose of fenfluramine, 0.4 mg/kg/day, with placebo in patients who were receiving stiripentol and either clobazam, valproate, or both. The 0.4 mg/kg/day dose accounted for a drug interaction between stiripentol and fenfluramine and was designed to approximate the 0.7 mg/kg/day dose evaluated in Study 1.
Long-term extension study
- 94% of patients who completed Study 1 or Study 2 participated in a long-term, flexible-dose, open-label extension study
- The study evaluated the safety and antiseizure activity of FINTEPLA
- Data on file, Zogenix, Inc.